Vertebrates, including mammals, must be prepared for defense against two distinct types of infectious insult. In the first instance, rapidly replicating micro-organisms such as bacteria, viruses, protozoa or fungi have the potential to overcome host defenses by sheer numbers. In the second, the body's protective barriers are breached by physical trauma as occurs when helminths and other metazoan parasites enter, migrate or exit their host. Infection by metazoan parasites is ubiquitous and seriously compromises host fitness.
In humans, helminths not only cause overt morbidity but contribute to anaemia and impaired physical and cognitive development, which can result in poor school or work performance. The powerful selective force of macroparasite infection in mammals is illustrated by direct effects on host fecundity energy consumption and ability to survive the winter. This selection pressure has led to the evolution of a host protective response, which includes the rapid repair of tissues to tolerate the damage caused by these macroparasites as well as resistance mechanisms to reduce parasite burden.
The type 2 arm of the immune system is essential for helminth control. It evolved from a progenitor wound healing response largely as a consequence of the exposure to tissue damaging macroparasites. During this dynamic vertebrate:macroparasite coevolutionary process, important additional characteristics were incorporated that together contribute both to increased tolerance, through enhanced wound healing, and to parasite resistance. In the course of evolution type 2 cytokines may have come to direct wound repair machinery not only towards tissue repair and reconstruction but also to containment, destruction, and expulsion of helminths and other macroparasites. For example, reparative cells or pathways may promote rapid encapsulation or efficient expulsion through the excess production of collagen or mucus, respectively. Thus, under the umbrella of type 2 immunity both wound repair and anti-worm effector pathways have evolved in tandem to mediate host protective helminth responses. Although type 2 immunity may include responses to a broad range of insults, it is the ability of helminth parasites to compromise host fitness that is likely to have driven the evolution of Th2 cells to control and direct the innate type 2 response towards reducing parasite numbers and more rapidly repairing the damage they inflict as they aggressively migrate through host tissues. This evolutionary view also encompasses the counter-regulatory nature of type 2 immunity, because a type 1 anti-microbial response directed at a large migrating worm would cause serious collateral damage and would need to be actively avoided and because effective wound repair requires suppression of inflammation to proceed. In other words, effective wound repair requires both the direct reconstruction of the injured tissue and suppression of pro-inflammatory responses.
In view of the foregoing, a solution which overcomes the above-described inadequacies and shortcomings in current wound repair techniques is desired. In particular, it would be desirable to develop a method that utilizes aspects of the type 2 immune elicited by helminth to promote tissue repair and wound healing.